Diabetic Kidney Alarm (DKA) Study

Every year over 86,000 children (0-14 years) worldwide are diagnosed with type 1 diabetes
(T1D) translating to a lifetime of exposure and risk for early death from cardiovascular
disease (CVD) and diabetic kidney disease (DKD). DKD, which manifests in children and
adolescents, remains the leading cause of renal failure and dialysis in the Western world
(4). While diabetic glomerulopathy has received significant attention from researchers,
determinants of tubular injury in diabetes are less well examined. Compared to glomerular
injury, tubular injury is known to associate better with renal function. The majority of
youth diagnosed with T1D in the US present with diabetic ketoacidosis (DKA), a condition
associated with risks factors for tubular injury including dehydration, metabolic acidosis
and acute glycemia. It is unknown whether DKA is associated with tubular injury. The
investigators published the first report showing that youth with established T1D have more
acidic urine and higher fractional excretion of uric acid (FeUA) than their non-diabetic
peers, which may predispose to UUA-mediated tubulopathy. Furthermore, T1D is associated with
vasopressin overactivity, and the investigators reported strong relationships between serum
copeptin, a reliable surrogate marker for vasopressin, and DKD in T1D. The overarching goals
of this study are to determine whether tubular dysfunction (elevated urine sodium,
bicarbonate and amino acids) and injury (elevated KIM-1, NGAL and MMP9) exist in DKA, whether
it is reversible and whether it is related to uricosuria and copeptin. The investigators
propose to study a cohort of youth (ages 3-18, n=40) with T1D who have serum and urine
collection at DKA diagnosis and 3-month follow-up.

Inclusion Criteria:

- New onset T1D and known T1D

- DKA (mild, moderate and severe DKA eligible)

- 3-17 years of age

- Toilet trained

- Boys and girls

- All ethnicities

- Initial presentation to Children's Hospital Colorado (CHCO) Main ED

Exclusion Criteria:

- Non-T1D etiology

- History of chronic kidney disease (eGFR <60ml/min/1.73m2) or dialysis dependent

- History of tubulopathy (e.g. Fanconi syndrome)

- Currently menstruating

- Patient visiting Colorado with plan to establish diabetes care outside of Colorado

- On ACE-inhibitors or angiotensin II-receptor blockers (ARB)

- On sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors)